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Acute Lymphoblastic Leukemia

What is Acute Lymphoblastic Leukemia?

Acute lymphoblastic leukemia is a cancer that begins in the bone marrow, which instead of producing healthy white blood cells will instead produce a high volume of transitional cells called lymphoblasts. Lymphoblasts develop from stem cells found in the bone marrow and mature into white blood cells called lymphocytes. In acute lymphoblastic leukemia, these lymphoblasts never progress to full white blood cells, and instead multiply and crowd other types of blood cells and platelets. This eventually moves from the bone marrow to the bloodstream and other parts of the body, causing low platelet count and easy bruising. Because ALL can spread throughout the bloodstream, it is likely to affect other areas and organs if not treated properly. 

The name of this disease describes its nature: “acute” means that it progresses rapidly, “lymphoblastic” refers to the cancerous lymphoblasts that never mature, and “leukemia” is a type of cancer that develops in the bone marrow and spreads to the blood. Acute lymphoblastic leukemia is also known as acute lymphocytic leukemia, due to lymphocytes being the name of the white blood cells that are not adequately made during this disease. Acute lymphoblastic leukemia can affect the two different types of white blood cells: B-cells and T-cells:

  • B-cells make antibodies and help fight infection. B-cell ALL accounts for 75% to 80% of ALL cases.

  • T-cells destroy germs and support other immune system cells

Cancer is the rapid growth of cells without proper direction. A cancer affecting white blood cells can be leukemia, which affects the blood and bone marrow, or a lymphoma, which primarily affects the blood, lymph nodes, and other organs but can sometimes affect bone marrow. In the case of ALL, the cancer originates in the bone marrow and thus it is categorized as leukemia.

 

 

 

Synonyms

  • Acute lymphocytic leukemia
  • Acute lymphoid leukemia

Acute lymphoblastic leukemia is a cancer that begins in the bone marrow, which instead of producing healthy white blood cells will instead produce a high volume of transitional cells called lymphoblasts. Lymphoblasts develop from stem cells found in the bone marrow and mature into white blood cells called lymphocytes. In acute lymphoblastic leukemia, these lymphoblasts never progress to full white blood cells, and instead multiply and crowd other types of blood cells and platelets. This eventually moves from the bone marrow to the bloodstream and other parts of the body, causing low platelet count and easy bruising. Because ALL can spread throughout the bloodstream, it is likely to affect other areas and organs if not treated properly. 

The name of this disease describes its nature: “acute” means that it progresses rapidly, “lymphoblastic” refers to the cancerous lymphoblasts that never mature, and “leukemia” is a type of cancer that develops in the bone marrow and spreads to the blood. Acute lymphoblastic leukemia is also known as acute lymphocytic leukemia, due to lymphocytes being the name of the white blood cells that are not adequately made during this disease. Acute lymphoblastic leukemia can affect the two different types of white blood cells: B-cells and T-cells:

  • B-cells make antibodies and help fight infection. B-cell ALL accounts for 75% to 80% of ALL cases.

  • T-cells destroy germs and support other immune system cells

Cancer is the rapid growth of cells without proper direction. A cancer affecting white blood cells can be leukemia, which affects the blood and bone marrow, or a lymphoma, which primarily affects the blood, lymph nodes, and other organs but can sometimes affect bone marrow. In the case of ALL, the cancer originates in the bone marrow and thus it is categorized as leukemia.

 

 

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While acute lymphoblastic leukemia is the most common type of cancer diagnosed in children, it is relatively rare and only accounts for less than half of 1% of total cancer diagnoses in the U.S. Most cases of ALL occur in children between the ages of 2 and 5 years old, and the risk declines after age 15 and then rises again in adults over 50 years of age. Overall, about 4 out of 10 cases of ALL develop in adults, but the death toll is higher in adult cases, with every 4 out of 5 deaths from ALL occurring in adult patients. The risk  of developing ALL in one’s lifetime is about 1 in 1000, slightly higher in people born genetically male than genetically females, and higher in white people than African Americans in the US.

 

Name Abbreviation
Acute lymphocytic leukemia ALL
Acute lymphoid leukemia ALL

The exact cause of acute lymphoblastic leukemia is still unknown, yet the current theory about the cause of this disease involves a genetic mutation or predisposition to the development of cancer, and then exposure to an infection or foreign agent. A genetic mutation could affect the body’s production of blood cells and cause unchecked growth of lymphoblasts that aren’t converted to white blood cells. An environmental exposure could be a viral infection, or exposure to previous cancer treatments. Further damage to cells with a mutation for rapid growth will often lead to the development of cancer. An increased risk of ALL is caused by exposure to previous cancer treatment, radiation, or other damage to your cells and tissues. This may account for some of the cases of ALL in older people who have had cancer before or received other treatments. In addition, certain genetic disorders such as Down syndrome have been associated with higher risk levels of acquiring ALL, and other rare diseases whose mutations may cause ALL include neurofibromatosis, Klinefelter syndrome, Fanconi anemia, Schwachman-Diamond syndrome, Bloom syndrome and ataxia telangiectasia. 

 

The physical signs and symptoms of acute lymphoblastic leukemia resemble that of a long term infection due to the low platelet and white blood cell count available to fight infection in the body. These symptoms can include bleeding gums, pain in bones or joints, prolonged fever, frequent infections, frequent or severe nosebleeds, lumps caused by swollen lymph nodes in and around the neck, armpits, abdomen, and groin, pale skin, shortness of breath, weakness and fatigue or general decrease in energy. The most common symptoms of ALL are prolonged flu-like symptoms, pain in the bones or joints, abnormal bleeding, or fatigue. Since these symptoms are often associated with other less serious conditions, it is suggested to seek medical care if symptoms similar to an infection persist for over two weeks. 

 

Name Description
Weakness and fatigue Weakness and fatigue
Anemia Anemia is a deficiency of hemoglobin.
Weight loss and/or loss of appetite Weight loss and/or loss of appetite
Enlarged lymph nodes, liver and/or spleen Enlarged lymph nodes, liver and/or spleen
Breathlessness Breathlessness
Excessive and unexplained bruising Excessive and unexplained bruising
Joint pain Joint pain
Bone pain Bone pain

Diagnosis consists of the following being true:

  • The complete blood count (CBC) is abnormal compared to a healthy count

  • More than 5% of the cells in the bone marrow are lymphoblasts (leukemia cells) that have not matured to white blood cells

  • There are signs and symptoms of leukemia, such as flu-like symptoms mentioned above

The tests used to determine a diagnosis of acute lymphoblastic leukemia aim to determine the number of white blood cells being produced by the body and if there are abnormal levels of lymphoblasts preventing normal white blood cell levels. These diagnostic tests include:

  • Complete blood count (CBC): blood drawn is checked for red and white blood cell count, content of hemoglobin and thus the amount of oxygen in the blood compared to normal levels

  • Blood chemistry studies: blood is analyzed for certain molecules that may be released by the organs during cases of cancer

  • Peripheral blood smear: analysis of the blood for lymphoblast cells, white blood cells, platelet cells, and changes in the shape of blood cells

  • Bone marrow aspiration and biopsy: extraction and removal of a piece of one’s bone marrow by inserting a hollow needle into the hip or breast bone and examining its contents under a microscope

  • Cytogenetic analysis: checking if the chromosomes in the extracted blood or bone marrow have certain abnormalities such as broken, missing, rearranged, or extra pieces of the chromosome

  • Immunophenotyping: a test that utilizes different markers, called antigens, given off by cancer cells that can be detected with dyes, antibodies, or other agents specifically designed to bind to them

Tests are also run to determine if the cancer has spread to other parts of the body. These can include the use of a chest x-ray, lumbar puncture, CT or MRI scan.

 

There are different types of treatment available for acute lymphoblastic leukemia, and these are used in various circumstances depending on the age of the individual, the progressive stage of the cancer, and any former or ongoing medical needs of the individual. Often, chemotherapy is the first line of treatment used for ALL. Clofarabine (Clolar) is approved to treat childhood ALL and shows promise in early studies of adults with this disease. Nelarabine (Arranon) is a newer drug that can be used to treat T-cell ALL. Chemotherapy consists of a 4 step treatment process that can take place over months or years and is designed to remove as many cancerous cells as possible. It is recommended to also  receive palliative care during chemotherapy to treat negative symptoms that may arise. The four stages of chemotherapy for leukemia such as ALL are the following: 

  1. Remission induction therapy - designed to destroy as many leukemia cells as possible, generally takes place in a hospital over 4-6 weeks

  2. Central nervous system-directed therapy - designed to remove leukemia cells from spinal fluid and prevent it from spreading throughout the body; this is applied throughout the different stages of therapy to prevent the cancer from spreading or metastasizing 

  3. Consolidation therapy - begins in remission stages of ALL, destroying any remaining cancerous cells and may involve high doses of chemotherapy being delivered at the hospital over several months

  4. Continuation or maintenance therapy - takes place outside of a hospital and may continue for several months or years to maintain healthy cells

Other treatment options are available to individuals with specific needs or diagnostic qualities. If the genetic mutations causing ALL are known and have reversible modulators, a targeted therapy can be applied to treat the source of the cancerous lymphoblasts. For example, tyrosine kinase inhibitors block a specific protein, tyrosine kinase, from converting stem cells into white blood cells, therefore slowing the progression of cancerous lymphoblasts. 

Immunotherapy is a new and ongoing treatment option for blood cancers. Monoclonal antibodies from an external donor, or T-cells from the individual with ALL, are modified to include a receptor protein that recognizes cancer cells in the bloodstream. The monoclonal antibodies bind to this cancer cell and “mark” it for destruction, but CAR-T cells (modified T-cells) can recognize and destroy cancer cells right away. 

Radiation therapy is the use of high energy x-rays or other forms of radiation directed to areas inside the body to destroy cancer cells. This treatment option is used especially if ALL has spread to brain or spinal fluid. Radiation can also be used to prepare the body for a stem cell transplant via bone marrow transplantation.

 

Bone marrow transplantation is more commonly used in adults with ALL, and is used to replenish healthy allogenic stem cells in the bone marrow. Healthy bone marrow stem cells from the individual with ALL prior to treatment or from a donor are stored until after chemotherapy or other treatments. After chemotherapy, the body works to regenerate cells that have been destroyed. In order to more quickly restore healthy white blood cells in the body, the healthy bone marrow stem cells are reinjected through an infusion.

 

Acute lymphoblastic leukemia has many treatment options available. However, given the acute (fast-acting) nature of this cancer, prognosis can worsen if treatment is not applied during early detection. The prognosis for ALL is slightly better for children than in adults, with about 4 out of 5 deaths from ALL occurring in adults. This may be due to the different nature of the disease as the body develops, or a child’s improved response to aggressive cancer treatment measures. Overall, the survival rate of ALL was recorded at about 71.3% chance of survival as of 2019.

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Leukemia & Lymphoma Society (LLS)

The Leukemia & Lymphoma Society (LLS) is the world's largest voluntary health organization dedicated to funding blood cancer research, education and patient services. The mission of LLS is to cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality of life of patients and their families. Since its founding in 1949, LLS has invested more than $600 million for research specifically targeting blood cancers.

03/20/2017

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Cords registry

CoRDS, or the Coordination of Rare Diseases at Sanford, is based at Sanford Research in Sioux Falls, South Dakota. It provides researchers with a centralized, international patient registry for all rare diseases. This program allows patients and researchers to connect as easily as possible to help advance treatments and cures for rare diseases. The CoRDS team works with patient advocacy groups, individuals and researchers to help in the advancement of research in over 7,000 rare diseases. The registry is free for patients to enroll and researchers to access.

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After these steps, the enrollment process is complete. All other questions are voluntary. However, these questions are important to patients and their families to create awareness as well as to researchers to study rare diseases. This is why we ask our participants to update their information annually or anytime changes to their information occur.

Researchers can contact CoRDS to determine if the registry contains participants with the rare disease they are researching. If the researcher determines there is a sufficient number of participants or data on the rare disease of interest within the registry, the researcher can apply for access. Upon approval from the CoRDS Scientific Advisory Board, CoRDS staff will reach out to participants on behalf of the researcher. It is then up to the participant to determine if they would like to join the study.

Visit sanfordresearch.org/CoRDS to enroll.

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Daughter diagnosed with deletion 4q13.1 at 24 months, also has leukemia diagnosed at 16 months.

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